Modified lentiviral globin gene therapy for pediatric β0/β0 transfusion-dependent β-thalassemia: A single-center, single-arm pilot trial

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING
Shiqi Li, Sikai Ling, Dawei Wang, Xiaoyuan Wang, Fangyuan Hao, Liufan Yin, Zhongtao Yuan, Lin Liu, Lin Zhang, Yu Li, Yingnian Chen, Le Luo, Ying Dai, Lihua Zhang, Lvzhe Chen, Dongjie Deng, Wei Tang, Sujiang Zhang, Sanbin Wang, Yujia Cai
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引用次数: 0

Abstract

β00 thalassemia is the most severe type of transfusion-dependent β-thalassemia (TDT) and is still a challenge facing lentiviral gene therapy. Here, we report the interim analysis of a single-center, single-arm pilot trial (NCT05015920) evaluating the safety and efficacy of a β-globin expression-optimized and insulator-engineered lentivirus-modified cell product (BD211) in β00 TDT. Two female children were enrolled, infused with BD211, and followed up for an average of 25.5 months. Engraftment of genetically modified hematopoietic stem and progenitor cells was successful and sustained in both patients. No unexpected safety issues occurred during conditioning or after infusion. Both patients achieved transfusion independence for over 22 months. The treatment extended the lifespan of red blood cells by over 42 days. Single-cell DNA/RNA-sequencing analysis of the dynamic changes of gene-modified cells, transgene expression, and oncogene activation showed no notable adverse effects. Optimized lentiviral gene therapy may safely and effectively treat all β-thalassemia.

Abstract Image

改良慢病毒球蛋白基因疗法治疗小儿 β0/β0 输血依赖型 β 地中海贫血症:单中心、单臂试验
β0/β0地中海贫血症是输血依赖型β地中海贫血症(TDT)中最严重的类型,目前仍是慢病毒基因疗法面临的挑战。在此,我们报告了一项单中心、单臂试点试验(NCT05015920)的中期分析,该试验评估了β-球蛋白表达优化和绝缘体工程化的慢病毒修饰细胞产品(BD211)在β0/β0 TDT 中的安全性和有效性。两名女童接受了 BD211 的输注,并接受了平均 25.5 个月的随访。两名患者的基因修饰造血干细胞和祖细胞移植成功并持续。在调理期间或输注后没有出现意外的安全问题。两名患者都实现了超过22个月的独立输血。治疗使红细胞的寿命延长了42天以上。对基因修饰细胞的动态变化、转基因表达和癌基因活化进行的单细胞DNA/RNA测序分析表明,没有发现明显的不良反应。经过优化的慢病毒基因疗法可安全有效地治疗所有β地中海贫血症。
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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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